小粒径氟尿嘧啶隐形泡囊的制备、表征及其抗癌作用评价  

Preparation,characterization and antitumor effects of fluorouracil-loaded small size stealth niosomes

作　　者：龚珠萍[1] 吕小燕[1] 杨红[1] 罗庚[1] 刘迪[1] 赵成龙[1] 邢溪溪 宋雪[1] 黄丽[1] 

机构地区：[1]苏州大学药学院,苏州215123

出　　处：《中国新药杂志》2015年第23期2740-2745,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金(81473166)

摘　　要：目的：制备小粒径氟尿嘧啶隐形泡囊给药系统,对其进行理化表征并研究其体内外抗癌作用。方法：采用溶剂注入法制备泡囊,经过形态、粒径、包封率和体外释放规律等物理性质考察,并通过对2种癌细胞的细胞毒性实验及对balb/c荷瘤鼠抑瘤实验评价其抗癌作用。结果：制得的泡囊为球形、平均粒径240.4 nm、Zeta电位为-68.37 m V、表面水化层厚度1.83 nm、包封率32.76%;泡囊的体外释放符合Weibull模型,在模拟正常体液中释药减缓（t1/2为游离氟尿嘧啶的3.47倍）。泡囊在体外对癌细胞的生长抑制作用显著,对细胞的IC_（50）降低为游离Fu的9.1%～18.4%（P〈0.01）。泡囊对balb/c荷瘤鼠的瘤增长抑制明显,抑瘤率由同浓度游离药物的19.58%增加至48.45%。结论：本实验制备的小粒径氟尿嘧啶泡囊性能好,缓释性能明显,细胞实验、动物实验均表明抗癌作用显著,是一种具有良好开发前景的新型微粒给药系统。Objective： To prepare small size niosome drug delivery system for 5-fluorouracil,characterize its physicochemical properties and study its antitumor effects in vitro and in vivo. Methods： The niosomes were prepared by solvent injection method,and characterized by investigation of their physical properties,such as morphology,particle size,encapsulation efficiency and in vitro release behavior. Antitumor effects were evaluated by cell toxicity test against two kinds of tumor cells in vitro and by tumor suppression test in tumor-bearing mice in vivo. Results： The average diameter of the prepared spherical niosomes was（ 240. 4 ± 10. 1） nm with Zeta potential of-68. 37 m V,FALT of 1. 83 nm and encapsulation rate of 32. 76%. The release profile in vitro could be described by Weibull distribution equation,and showed an obvious sustained release feature in simulated normal body fluid as indicated by a release t1 /2of 3. 47 times as long as that of the free drug. Cell toxicity test demonstrated that the niosomes had significant inhibitory effect against tumor cell growth when compared with the free drug,with IC50 decreased to 9. 1% ～ 18. 4% of the free drug（ P 〈0. 01）. The niosomes significantly inhibited tumor growth in the tumor-bearing mice. The tumor growth inhibition rate increased to 48. 45% from 19. 58% for the free drug of the same concentration. Conclusion： The prepared fluorouracil-loaded niosomes have desirable physical properties and significant drug sustained release feature and demonstrated obvious antitumor effects in the cell tests and animaltests,which provides a promising candidate of novel microparticul antitumor drug delivery system.

关 键 词：氟尿嘧啶 小粒径泡囊 物理性质 细胞毒性 抗癌作用 

分 类 号：R979.1[医药卫生—药品]